The displacement of the acetoxy group of a cephalosporin by a sulfur nucleophile is a known reaction (U.S. Pat. No. 3,278,531). This patent and other publications (J. D. Cocker, J. Chem. Soc., 1965, 5015) teach that the reaction occurs only in an aqueous medium. Practical displacements have utilized a salt of the cephalosporanic acid in water along with the sulfur nucleophile or its salt at pH 5-8. The combination of aqueous medium, elevated temperature (35.degree.-70.degree. C.), and near neutral to basic pH are generally destructive of much of the cephalosporin nucleus, and products prepared in this manner often require extensive purification. Attempts to conduct the displacement on cephalosporanic acids in water at lower pH (pH 2-3) lead to substantial lactone formation, a side-reaction that dramatically lowers the yield of desired product.